2- Phenylethylamine derivatives

Phenylethylamine derivatives epinephrine, DOPA, 2-amino-3-hydroxy-3-phenyl-propanol, ephedrine Vitamin D2 and D3 Doxorubicin... 

Venlafaxine (48) is a stmcturaHy novel phenylethylamine derivative that strongly inhibits both noradrenaline and serotonin reuptake. It lacks anticholinergic, antihistaminergic, and antiadrenergic side effects. As compared to placebo, most common adverse events are nausea, somnolence, dizziness, dry mouth, and sweating. Venlafaxine-treated patients also experienced more headaches and nausea, but less dry mouth, dizziness, and tremor than patients treated with comparator antidepressants. 

As already stated, the number of substances made by chemists for pharmacological examination as possible sympathomimetic amines is enormous and the literature voluminous. Fortunately the latter has been reviewed from time to time, and most recently in the symposium in which Hartung dealt with the correlation of structure and pharmacological action in )3-phenylethylamine derivatives, which includes the more impor-... 

Seven groups of these drugs can be separated based on their various chemical f structures (a) lysergic acid derivatives, of which lysergide (LSD) is the prototype (b) phenylethylamine derivatives, of which 3,4,5-trihydroxyphenylethylamine (mescaline) is the prototype (c) indolealkylamines, such as 4-phosphorodi-methyltryptamine (psilocybin) (d) other indolic derivatives, such as the harmine... 

Competitive inhibitors bind to specific groups in the enzyme active site to form an enzyme-inhibitor complex. The inhibitor and substrate compete for the same site, so that the substrate is prevented from binding. This is usually because the substrate and inhibitor share considerable stmctural similarity. Catalysis is diminished because a lower proportion of molecules have a bound substrate. Inhibition can be relieved by increasing the concentration of substrate. Some simple examples are shown below. Thus, sulfanilamide is an inhibitor of the enzyme that incorporates j9-aminobenzoic acid into folic acid, and has antibacterial properties by restricting folic acid biosynthesis in the bacterium (see Box 11.13). Some phenylethylamine derivatives, e.g. phenelzine, provide useful antidepressant drags by inhibiting the enzyme monoamine oxidase. The cA-isomer maleic acid is a powerful inhibitor of the enzyme that utilizes the trans-isomer fumaric acid in the Krebs cycle. 

The hallucinogens generally fall into two chemical classes. The indole alkylamines include LSD, psilocybin, psilocin, dimethyltryptamine (DMT), and diethyltrypta-mine (DET), all of which are structurally similar to serotonin. The other chemical subclass of hallucinogens contains phenylethylamine derivatives such as mescaline, MDMA, MDA, and DOM (dimethoxymethyl amphetamine). A related stimulatory hallucinogen, PCP, is a piperidine analogue that produces unique effects. 

Figure 6.35 ricinine PLP-dependent decarboxylation of L-tyrosine gives the simple phenylethylamine derivative... 

Direct amidation can be carried out if an aromatic compound is heated with a hydroxamic acid (34) in polyphosphoric acid, but the scope is essentially limited to phenolic ethers.The reaction of an aromatic compound with aniline, BU4NF and KMn04 led to the diarylamine. The formation of hydroindole derivatives was accomplished by reaction of a A-carbamoyl phenylethylamine derivative with phenyliodine (III) diacetate, followed by Bu4NF. Direct amidation via ipso substitution by nitrogen was accomplished when a A -methoxy arylethylamide (35) was... 

Gesellschaft Manufacture of Trialkoxy-derivatives Phenylethylamine Derivatives 1931 GB 360,266... 

Amicar aminocaproic acid, amicarbalide [ban. inn] is a veterinary antiprotozoal. amicycline [inn, usan] is a (tetracycline) antibiotic, which can be used as a broad-spectrum antibacterial. amidefrine mesilate amidephrine. amidephrine [ban] (amidephrine mesylate [usan] amidefrine mesilate [inn]) is a phenylethylamine derivative. 

Structurally, mazindol is related to the tricyclic antidepressants it is not a phenylethylamine derivative. Like sibutramine, it inhibits the reuptake of noradrenaline and dopamine into presynaptic neurones rather than promoting their release. It also inhibits the reuptake of serotonin. Mazindol was introduced into clinical practice in the 1970s. Clinically, it reduces hunger awareness and lowers food intake. A number of double-blind clinical trials have shown mazindol 2 mg daily to be significantly more ef-... 

A series of isoquinoline alkaloids and phenylethylamine derivatives from Cactaceae has been analyzed on silica gel14 (Table 6.2). Addition of alkali to the mobile phase was found to reduce tailing. The system decsribed could also be used for semipreparative purposes. 

Table 5.3 Enantioseparation of 1-phenylethylamine derivatives with mandelic acid.

Naphfhylglycolic acid was also effective for the enantioseparation of a wide variety of p-substituted 1-phenylethylamine derivatives (Table 5.5) [13]. Figure 5.11 shows the typical crystal structures of a pair of the diastereomeric salts. The crystal structures are quite similar to each other, suggesting that another factor is contributing to the stabilization of the diastereomeric salt crystals odier than hydrogenbonding and van der Waals interactions. Precise examination of the crystal struc-... 

Table 5.5 Enantioseparation of 1 -phenylethylamine derivatives with 2-na p hthyl glycol ic acid.

Allan, R.D., and Tran, H.W., Facile synthesis of P-phenylethylamine derivatives related to baclofen via aziridine ring opening, Aust. J. Chem., 43, 1123, 1990. 

Figure 9.11 Chiral a phenylethylamine derived phosphine phosphoramidite ligands (PEAPhos) developed within our group.

One of the most powerful methods for the construction of tetrahydroisoquinoline systems is the Pictet-Spengler cyclisation. The reaction consists of the condensation of a b-phenylethylamine derivative with a carbonyl compound, generating an imine (Schiffs base), which undergoes cyclisation via an intramolecular electrophilic aromatic substitution yielding the isoquinoline derivative. The Pictet-Spengler reaction is traditionally carried out in a protic solvent with acid catalysts, usually acetic acid or trifluoroacetic acid. 

The quinazolines, vasicinone (23 R = OH), vasicine (24 R = H, R = OH) and vasicinol (24 R = R = OH) have been obtained from Sida cordifolia L. (Malvaceae). These are the first alkaloids, apart from j8-phenylethylamine derivatives, to have been isolated from this genus. 

The reader who is not well acquainted with the extensive and controversial literature of deamination mechanisms of the last five decades may have the impression from our relatively detailed review of White et al. s recent paper and of the related work of Collins group that the dominant role of ion pairing in deaminations was not clearly recognized earlier. This is by no means the case. The paper of White s group (1992b) was chosen for this discussion because it combines and expands previous partial results with 1-phenylethylamine derivatives for which mechanistic conclusions are not disguised by a multitude of products as they are illustrated in the introductory Scheme 7-1. 

Dopamine -hydroxylase catalyzes the side-chain hydrox-ylation of dopamine and other phenylethylamine derivatives. Ascorbic acid serves as a specific electron-donating cofactor. The enzyme from bovine adrenal glands contains and a smaller amount of Cu. When the enzyme oxidizes ascorbate to dehydroascorbate, most of the is reduced to Cu Added substrate is hydroxylated, and Cu is reoxidized to Cu This indicates that most of the protein-bound Cu undergoes cyclic reduction and oxidation during hydroxyhtion. The results also rule out an oxygen-carrier function for ascorbate. The possibility that a p-substituted hydroperoxide of the substrate is formed as an intermediate in the reaction has been examined with the use of 13,13 -tritium-labelled substrate. The results indicate that such an intermediate is unlikely. 

Symposium on Sympathomimetic agents. Clinical uses H. Gold Imidazole derivatives C. R. Scholz 8-Phenylethylamine derivatives W. H. Hartung Pharmacological methods M. L. Tainter Deamination of sympathomimetic amines K. H. Beyer and Helen S. Morrison Phenylpropyl and phenilisopropyl-amines B. E. Graham, G. F. Cartland and E. H. Woodruff, Ind. Eng. Chem.,... 

Blackman, A. J., Fu, S.-L. A y0-phenylethylamine-derived possible biosynthetic precursor to the amathamides, alkaloids from the bryozoan Amathia wilsoni. J. Nat. Prod. 1989, 52, 436-438. 

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